Bowton David L, Dmitrienko Alexei A, Israel Elliot, Zeiher Bernhardt G, Sides Gregory D
Department of Anesthesiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1009, USA.
J Asthma. 2005 Feb;42(1):65-71. doi: 10.1081/jas-200044748.
The possible roles of secretory phospholipases A2 (sPLA2) in asthma include the release of arachidonic acid from cellular membranes, generation of lysophospholipids, sPLA2-mediated activation of cPLA2 with increased leukotriene production, and surfactant degradation. LY333013 is a potent inhibitor of sPLA2. This study examined the impact of two doses of LY333013 vs. placebo on allergen-induced bronchoconstriction following inhaled allergen challenge in atopic asthmatics. Fifty subjects were randomly assigned to treatment, and 40 subjects completed the study. A double-blind, placebo-controlled, random order, crossover study design was used. LY333013 had no impact on the primary outcome variables of the areas under the FEV1 response curve early (0-3 hours) (AUC(early)) and late (3-8 hours) (AUC(Iate)) following inhaled allergen challenge. No significant drug-related adverse effects were observed. The response to inhaled allergen challenge was reproducible and confirms the utility of this technique as a model in which to screen compounds for further testing in asthmatic patients.
分泌型磷脂酶A2（sPLA2）在哮喘中可能发挥的作用包括从细胞膜释放花生四烯酸、生成溶血磷脂、sPLA2介导的胞质型磷脂酶A2（cPLA2）激活并增加白三烯生成以及表面活性剂降解。LY333013是一种有效的sPLA2抑制剂。本研究在特应性哮喘患者吸入变应原激发后，考察了两剂LY333013与安慰剂相比对变应原诱导的支气管收缩的影响。50名受试者被随机分配接受治疗，40名受试者完成了研究。采用双盲、安慰剂对照、随机顺序、交叉研究设计。LY333013对吸入变应原激发后早期（0 - 3小时）FEV1反应曲线下面积（AUC(early)）和晚期（3 - 8小时）（AUC(late)）的主要结局变量没有影响。未观察到明显的药物相关不良反应。对吸入变应原激发的反应具有可重复性，并证实了该技术作为一种模型用于筛选化合物以便在哮喘患者中进一步测试的实用性。
